Herker Eva, Jungwirth Helmut, Lehmann Katharina A, Maldener Corinna, Fröhlich Kai-Uwe, Wissing Silke, Büttner Sabrina, Fehr Markus, Sigrist Stephan, Madeo Frank
Institute for Physiological Chemistry, University of Tübingen, Hoppe-Seyler-Strasse 4, 72076 Tübingen, Germany.
J Cell Biol. 2004 Feb 16;164(4):501-7. doi: 10.1083/jcb.200310014.
During the past years, yeast has been successfully established as a model to study mechanisms of apoptotic regulation. However, the beneficial effects of such a cell suicide program for a unicellular organism remained obscure. Here, we demonstrate that chronologically aged yeast cultures die exhibiting typical markers of apoptosis, accumulate oxygen radicals, and show caspase activation. Age-induced cell death is strongly delayed by overexpressing YAP1, a key transcriptional regulator in oxygen stress response. Disruption of apoptosis through deletion of yeast caspase YCA1 initially results in better survival of aged cultures. However, surviving cells lose the ability of regrowth, indicating that predamaged cells accumulate in the absence of apoptotic cell removal. Moreover, wild-type cells outlast yca1 disruptants in direct competition assays during long-term aging. We suggest that apoptosis in yeast confers a selective advantage for this unicellular organism, and demonstrate that old yeast cells release substances into the medium that stimulate survival of the clone.
在过去几年中，酵母已成功成为研究凋亡调控机制的模型。然而，这种细胞自杀程序对单细胞生物的有益作用仍不清楚。在此，我们证明，按时间顺序老化的酵母培养物死亡时表现出典型的凋亡标志物，积累氧自由基，并显示半胱天冬酶激活。通过过表达YAP1（氧应激反应中的关键转录调节因子），可强烈延迟衰老诱导的细胞死亡。通过缺失酵母半胱天冬酶YCA1破坏凋亡，最初会导致老化培养物的存活率提高。然而，存活细胞失去了再生长的能力，这表明在没有凋亡细胞清除的情况下，预受损细胞会积累。此外，在长期老化的直接竞争试验中，野生型细胞比yca1破坏株存活时间更长。我们认为，酵母中的凋亡赋予了这种单细胞生物选择性优势，并证明老化的酵母细胞会向培养基中释放刺激克隆存活的物质。
